This application proposes continuation of the Southern Community Cohort Study (SCCS), a landmark investigation tracking the cancer and other disease experience of a cohort of nearly 86,000 adults age 40-79 at cohort entry. By design, two-thirds of the cohort was chosen to be African American, the remainder predominantly non-Hispanic white. The higher proportion of blacks helps remedy the underrepresentation of African Americans in health studies and provides a basis for evaluation of cancer risk factors and outcomes among blacks, while the enrollment of whites enables direct comparisons of black-white differences and assessment of determinants of health disparities. Recruitment took place during 2002-2009 across 12 southern states mainly at Community Health Centers (CHCs), institutions providing basic health and preventative services in underserved areas. Our recruitment strategy resulted in the SCCS comprising a vulnerable segment of the American population at elevated cancer risk seldom if ever included in large numbers in other cohorts. Associating with CHCs also facilitated creation of the unique SCCS Biospecimen Repository, with bloods obtained and stored for approximately 40,000, mouth cells for 39,000, urines for 24,000 and DNA available for nearly 90%. No other cohort has a collection of baseline blood, buccal cell, and urine specimens from African Americans as comprehensive as the SCCS. The SCCS up until now has been funded via an initial and two competing renewal R01 grants. Here, in the first application under the U01 cancer cohort infrastructure mechanism, we seek funding to continue the operational aspects of this highly successful study. The SCCS is poised to produce even greater benefit in the coming years as the cohort matures and larger numbers of cancer events occur. We propose to continue both passive (via linkage with national mortality, Centers for Medicare and Medicaid Services, state cancer registries and other health record databases) and active (via questionnaire survey) follow up of the cohort. In addition, we propose not only to maintain and make available for research the collected biologic samples, but also to enhance our Biospecimen Repository by newly collecting stool specimens from a projected 22,000 participants and tumor blocks from incident cancer cases. The stool samples will enable future study of fecal biomarkers and of gut microbiota (we believe for the first time in any cancer cohort of African Americans), and the tumor tissue specimens future study of somatic mutations in cancer risk and outcome. The Repository has been exceptionally important to date in genetic and molecular studies, since the SCCS provides one of the few resources available for discovery-stage analyses and for independent replication of findings in an African American population. Continuation of the SCCS will enable full utilization of the investment made thus far in this unique national resource and enhance its richness. The follow up of the cohort will accrue additional cancer and other disease outcomes enabling critical hypothesis-driven research (to be funded separately) into the causes of cancer among African Americans and the determinants of disparities among underserved groups.